ISSN (print) 1997-6933     ISSN (online) 2500-2139
Vol. 16 No. 2 (2023), CLINICAL TRIALS
Vol. 16 No. 2 (2023)
CLINICAL TRIALS

The Prognostic Value of Somatic Mutations of Epigenetic Regulation Genes in Acute Myeloid Leukemias in Real-World Clinical Practice: Results of an Observational Non-Interventional Prospective Interregional Study

Published 20.02.2024
Aleksina Alekseevna Shatilova
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
I.G. Budaeva
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
A.V. Petukhov
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
S.A. Silonov
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
A.E. Ershova
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
T.S. Nikulina
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
Yu.D. Matvienko
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
Yu.V. Mirolyubova
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
K.V. Bogdanov
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
L.V. Anchukova
Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002
Yu.S. Neredko
Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya ul., Stavropol, Russian Federation, 355001
S.Yu. Tyasko
Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya ul., Stavropol, Russian Federation, 355001
O.E. Ochirova
NA Semashko Republican Clinical Hospital, 12 Pavlova ul., Ulan-Ude, Russian Federation, 670031
A.G. Karpova
NA Semashko Republican Clinical Hospital, 12 Pavlova ul., Ulan-Ude, Russian Federation, 670031
E.R. Vasil’eva
Perm Krai Clinical Hospital, 85 Pushkina ul., Perm, Russian Federation, 614990
O.D. Serdyuk
Clinical Oncology Dispensary No. 1, 146 Dimitrova ul., Krasnodar, Russian Federation, 350040
D.A. Yaskulskii
Clinical Oncology Dispensary No. 1, 146 Dimitrova ul., Krasnodar, Russian Federation, 350040
D.V. Bukin
Regional Clinical Hospital, 105 Peterburgskoe sh., Tver, Russian Federation, 170036
Yu.A. Alekseeva
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
E.G. Lomaia
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
L.L. Girshova
VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341
2023-2
PDF_2023-16-2_174-185 (Russian)

Keywords

acute myeloid leukemias
IDH
DNMT3A
ASXL1
epigenetic regulation genes

How to Cite

Shatilova A.A., Budaeva I.G., Petukhov A.V., Silonov S.A., Ershova A.E., Nikulina T.S., Matvienko Y.D., Mirolyubova Y.V., Bogdanov K.V., Anchukova L.V., Neredko Y.S., Tyasko S.Y., Ochirova O.E., Karpova A.G., Vasil’eva E.R., Serdyuk O.D., Yaskulskii D.A., Bukin D.V., Alekseeva Y.A., Lomaia E.G., Girshova L.L. The Prognostic Value of Somatic Mutations of Epigenetic Regulation Genes in Acute Myeloid Leukemias in Real-World Clinical Practice: Results of an Observational Non-Interventional Prospective Interregional Study. Clinical Oncohematology. 2024;(2):174–185. doi:10.21320/2500-2139-2023-16-2-174-185.
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Abstract

Aim. To assess the rate of DNMT3A, IDH1, IDH2, and ASXL1 gene mutations and their effect on the prognosis both as isolated findings and in combination with well-known chromosomal aberrations and gene mutations in newly diagnosed acute myeloid leukemia (AML) patients from some regions of the Russian Federation.

Materials & Methods. The study enrolled 83 patients with newly diagnosed AML from 22 regions of the Russian Federation, who underwent molecular genetic examination for detecting IDH1 (R132), IDH2 (R140), ASXL1, and DNMT3A gene mutations with droplet digital PCR and Sanger sequencing methods.

Results. The mutation rate in DNMT3A was 16.7 %, in IDH1 (R132) it was 6 %, in IDH2 (R140) it was 9.6 %, and in ASXL1 it was 6 %. The R140 mutation in IDH2 correlated with the older age of patients. The mutations in IDH1 (R132), IDH2 (R140), and DNMT3A showed a significant association with mutated NPM1. The mutations in IDH1 (R132), IDH2 (R140) were reported to occur significantly more often in patients with normal karyotype. The IDH1 (R132) and IDH2 (R140) mutations appeared to have a favorable effect on AML prognosis, which is most likely to be associated with a high rate of their compatibility with NPM1 mutation. The mutated type of DNMT3A had a negative effect on overall survival of patients with NPM1 mutation. The mutation in ASXL1 also appeared to be an unfavorable prognostic factor for overall survival of patients with wild type NPM1.

Conclusion. A high rate of mutation occurrence in epigenetic regulation genes as well as the prognostic potential of these mutations in AML necessitate the need for determining the mutation status of DNMT3A, IDH1, IDH2, and ASXL1 in the context of primary diagnosis in real-world clinical practice.

PDF_2023-16-2_174-185 (Russian)

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